The long term goals of our research are to develop new formulations of therapeutically important drugs using cochleates as the delivery vehicle. Such formulations would have an improved route of delivery (oral rather than injectable to improve ease of administration and to reduce adverse effects of parenteral therapy), and lower toxicity, thereby improving the safety profile of drugs. The SBIR Phase I advanced the development of a new formulation of amphotericin B (AmB) that has low toxicity and allows the oral delivery of AmB. Oral amphotericin B cochleates showed excellent activity in murine models of clinically relevant invasive fungal infections: Disseminated candidiasis, disseminated aspergillosis, and central nervous system cryptococcosis. The overall objective of this SBIR Phase II is to further develop this new AmB cochleate formulation for the following target indications: 1) Treatment of azole-susceptible and azole-resistant oropharyngeal and esophageal candidiasis in immunosuppressed patients, 2) empiric therapy for presumed fungal infection in febrile, neutropenic patients, 3) treatment of selected patients with proven or probable invasive infections due to Aspergillus species, Candida species, and other life-threatening invasive fungal infections. To this end the following specific aims will be investigated: 1. To optimize cochleate AMB formulations (CAMB) as a commercially viable human therapeutic by testing CAMB prepared with less expensive raw materials (mainly phosphatidylserine) and simplified protocols. 2. To perform preclinical studies in a higher animal model. 3. To determine the mechanism of drug delivery mediated by cochleate 4. To initiate Phase I trials with CAMB in humans PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE